ANALYSIS OF RELATIVE CONFIGURATION OF ACY CLIC COMPOUNDS BASED ON LONG-RANGE CARBON-PROTON COUPLING-CONSTANTS DETERMINED BY 2-DIMENSIONAL NMR

A new NMR methodology was devised for configurational assignments of a cyclic structures in natural products or synthetic compounds. Conventi onal methods based on NOEs often suffer from the ambiguity in assignin g the configurations of compounds with acyclic structures and conforma tional alternation. Unlike these NOE analyses, the new methodology is based on the dihedral angle dependency of longrange carbon-proton coup ling constants ((2,3)J(C,H)) The combination of the coupling constants ((2,3)J(C,H), (3)J(H,H)) which are categorized to large, medium, or s mall allows to determine the relative stereochemistry among adjacent a symmetric centers or those separated by a methylene group. Hetero half -filter TOCSY (HETLOC) was shown to be the most effective for measurin g (2,3)J(C,H) Of protonated carbon system. For structures with quatern ary carbons or weakly coupling protons, in which TOCSY in HETLOC fails to correlate relevant protons, phase-sensitive HMBC (HMQC optimized f or long-range coupling) worked effectively. To evaluate the utility of the method in structural analysis of natural products, the relative c onfigurations of acyclic portions of maitotoxin, the largest secondary metabolite known to date, were assigned by this method, which evident ly demonstrated the validity of (2,3)J(C,H) in the configurational and conformational analysis of organic compounds.